Acute graft versus host disease (GVHD) is a leading cause of death following allogeneic bone marrow transplantation. Current modalities for the prevention and treatment of GVHD are not entirely effective, and lack specificity for the T lymphocytes that cause the disease. Recent results from this and other laboratories have suggested that analogs of deoxyadenosine and deoxyguanosine resistant to cellular catabolism can inhibit selectively the proliferation and/or survival of mature T lymphocytes, without severely harming other cell types. The proposed experiments will use novel enzymatic and cell culture systems for the synthesis and identification of T cell specific anti-metabolites. The ability of the individual nucleosides to alter the generation of allospecific cytotoxic T cells will be tested. The most promising new compounds will be applied for the prevention and treatment of acute GVHD in experimental animals, and eventually in patients with leukemia who receive allogeneic bone marrow transplants.